Medical implants for use in human and animal bodies is known in the arts to serve numerous purposes, both short-term and long-term. One common complication associated with medical implants is infection at the implantation site. Implant related infection is managed by a number of different means, including use of prophylactic systemic antibiotics administered to the patient during set periods before and after implantation surgery. However, infection of the host site remains a common problem, most often requiring a second surgery to remove the implant. The reason for implant removal is that when an infection occurs, the implant acts as the site preferred by the invading bacteria to colonize. When bacterial floras thus colonize the implant, they are extremely resistant to eradication via delivery of antibiotic drugs through systemic means (such as oral or intravenous). The only means to manage such an infection is revision surgery to remove the colonized implant, to be replaced by another implant system. Revision surgery is associated with all of the complications of any surgery, which include infection. Additionally, the patient body now has to deal with morbidities of two surgeries. Other undesirable aspects of revision surgery include blood loss and thrombosis. Revision surgery is also associated with greater risk of implant failure, and the medical prognosis of a revision surgery is never as good as primary surgery. Revision surgery is more costly than primary surgery, and it requires additional longer recovery time for the patient to become fully functional, which can result in loss of productivity. As can be seen in the preceding, revision surgery due to implant site infection is a major medical problem for the patient, and a major drain on the cost of treatment. A technology that reduces or eliminates implant related infection will make an important positive contribution to the patient's well being and the economics of delivering medical care.
It is well known in medicinal arts that the metal silver and its compounds are good antibacterial agents. As such, silver and its compounds are routinely used to treat superficial skin infections. Silver compounds are typically administered to a new born baby's eyes to ward off potential infections. One major advantage of silver compounds over traditional antibiotic drugs is that infectious bacteria do not form resistance to silver. Drug resistant bacteria are a major cause for concern in the field of treating infections. Silver compounds, therefore, have the potential for preventing bacterial infections in medical implants, without the risk of developing resistant strains of bacteria.
Numerous attempts have been made in the past to incorporate metallic silver and/or its compounds into the outer surfaces of medical implants. These attempts and limitations thereof are summarized below.
Silver can be plated (coated) onto medical implants by any number of means known in the arts, including electroplating, electro-deposition, and painting with an organic polymer carrier. Other techniques for coating include chemical vapor deposition (CVD) and physical vapor deposition (PVD). CVD and PVD techniques are very expensive and require highly sophisticated, controlled manufacturing processes. All of these coating techniques have limited use in implants because the biological interface, i.e., the interface between the implant and the host tissue is completely different for the coated implant versus the uncoated implant. This limitation can have a profound impact on the success of the medical implant, whose biological interface is usually engineered for integration with the host tissue. This need for the implant biological interface to have antimicrobial properties simultaneous with tissue integration properties forms an important aspect of this invention as will be shown later.
Attempts have been made to “implant” ions of silver onto surfaces of medical implants. This technique utilizes energetic beams (high velocity) of ionized silver which are impinged upon the surface of the implant. This technique is referred to as “ion implantation”. Silver ion implantation affects only a very thin surface layer (typically in the range of nanometers thick), and therefore has limited use for long-term effectiveness against infectious agents. The “implanted” silver ions may be so well incorporated into the medical implant surface that very little would leach out into the surrounding tissue for effective kill of bacteria. Similar limitations are present in the technique called “ion beam assisted deposition” (IBAD). Ion implantation techniques are also very expensive and require sophisticated, controlled manufacturing processes.
It was discussed previously that the biological interface of the implant, effectively the surface of the implant in contact with host tissue, is typically engineered to integrate with the host tissue. A common surface engineering technology used in medical implants, particularly bone contacting orthopaedic, spinal, and dental implants is hydroxyapatite (HA) coating.
Hydroxyapatite (HA) coatings are applied to medical implants using a number of different methods, including plasma spray, electrodeposition, solution precipitation, and sol-gels methods. Attempts have also been made to incorporate silver into HA. Mainly, the prior art has used the following two different methods to provide a silver-doped HA coating:
One method of incorporating a silver derivative into HA includes the steps of sequentially applying layers of stable silver oxide and HA powder to an implant. However, this method does not form a homogeneous silver-doped HA coating. Consequently, coverage is not uniform, and ion release is not steadily maintained after implantation. Even if the silver oxide is mixed with the HA powder prior to plasma-spraying, the oxide cannot chemically react and combine with conventional HA powder to form a homogenous formulation.
The second method has been to soak an implant having a hydroxyapatite coating in a silver nitrate solution for approximately 24 hours and then dry the implant, in air or an inert environment. This method relies on applying silver into an implant that has already been coated with HA. This post hoc method has the potential of perturbing the physical and mechanical characteristics of the existing HA coating, which may not be desirable from the stand-point of HA attachment to the substrate medical implant. Additionally, this technique does not allow sufficient silver nitrate to soak deep into the HA coating. HA coatings on medical implants can range in thickness from a few to many hundreds of microns. Incorporation of silver by this method requires an ion exchange reaction between silver nitrate and HA coating. This ion-exchange reaction only occurs at the outer surface, where the HA coated implant makes contact with silver nitrate solution. Therefore, although silver is incorporated throughout the HA matrix at the surface, it is not incorporated into the HA matrix at the full thickness of the HA coating. Because silver is incorporated only at the surface and near surface region of the HA coating (and not throughout the thickness), the release of silver ions into the host tissue is likely to be shortlived; that is release of silver ions will not be sustained for very long periods required to ward-off infections a few months after implantation. Moreover, the ion exchange reaction requires careful control of the pH of the silver nitrate solution. The ideal pH of the silver nitrate solution may not be amenable to preservation of the HA structure already coated on the implant. In such a method, the HA coating attachment to the substrate medical implant may be compromised during the soaking process if the pH of the silver salt solution is not controlled.
The preceding discussion shows the limitations of prior art methods of incorporating silver and its compounds into the biological interfaces of medical implants. There is a need for commercially viable means of achieving antimicrobial coatings of medical implants. The ideal medical implant with antimicrobial properties would be such that the manufacturing of the same would not deviate from currently practiced manufacturing processes such as plasma spray.